This research project is designed to discover the mechanisms by which urate crosses cell and tissue barriers in man. The problem is being pursued from a number of different aspects. Isotopic experiments in mongrel and Dalmatian dogs are in progress to study the metabolism and excretion of both urate and its principal metabolite, allantoin. Such studies indicate that dog kidneys produce as well as excrete urate. If such a process occurs in man, all present concepts of uric acid excretion must be drastically revised. In a very different approach to the problem, we have examined the rate of exchange of urate and other small molecules betwee plasma and synovial fluid across both normal and diseased synovial membranes in man. This work has led to a new concept to explain the predisposition of gouty arthritis for joints which have been damaged by degenerative joint disease. A third area of study has concerned the interaction of urate and formaldehyde in vitro. New reaction products have been identified which may resemble similar compounds in vivo. Lastly, a new method of assessing human uric acid excretion has been developed. The new technique is much simpler and more reliable than existing methods. This new tool should be of great value in the diagnosis and management of patients with gout.